Click chemistry functionalized polymeric nanoparticles target corneal epithelial cells through RGD-cell surface receptors.

Department of Chemistry, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Room 514, Toronto, Ontario M5S3E1.

Bioconjugate chemistry 2009 Jan

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Self-assembled polymeric nanoparticles modified with targeting ligands on the surface provide a means for localized cell delivery. To gain greater insight into the possibility of derivatizing poly(2-methyl-2-carboxytrimethylene carbonate-co-D,L-lactide) (poly(TMCC-co-LA)) nanoparticles using the Huisgen's 1,3 dipolar cycloaddition reaction, we synthesized amphiphilic copolymers comprising a hydrophobic poly(TMCC-co-LA) backbone and a hydrophilic poly(ethylene glycol) (PEG) pendant chain. By coupling amine-terminated PEG-azide to the carboxylic acid group of the poly(TMCC-co-LA) via EDC chemistry, an amphiphilic copolymer was formed. The poly(TMCC-co-LA)-g-PEG-N3 self-assembled in aqueous solution and presented azide groups on the surface of the nanoparticles. Alkyne-modified KGRGDS peptides were synthesized and coupled to the azide-functionalized nanoparticles via Huisgen's 1,3 dipolar cycloaddition, which was catalyzed by copper sulfate and sodium ascorbate in aqueous solution. Using coumarin-modified lysine (K) of the KGRGDS peptide, fluorescence was used to determine that there were approximately 400 peptides bound to each nanoparticle. The bioactivity of the GRGDS nanoparticle was confirmed with a competitive cell attachment assay using rabbit corneal epithelial cells. This GRGDS-nanoparticle system may be suitable for targeted drug delivery.

Citation

Jiao Lu, Meng Shi, Molly S Shoichet. Click chemistry functionalized polymeric nanoparticles target corneal epithelial cells through RGD-cell surface receptors. Bioconjugate chemistry. 2009 Jan;20(1):87-94